Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pone.0006104
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dc.titleAbsence of leucine zipper in the natural FOXP3Delta2Delta7 isoform does not affect dimerization but abrogates suppressive capacity
dc.contributor.authorMailer R.K.W.
dc.contributor.authorFalk K.
dc.contributor.authorRötzschke O.
dc.date.accessioned2020-03-18T05:52:05Z
dc.date.available2020-03-18T05:52:05Z
dc.date.issued2009
dc.identifier.citationMailer R.K.W., Falk K., Rötzschke O. (2009). Absence of leucine zipper in the natural FOXP3Delta2Delta7 isoform does not affect dimerization but abrogates suppressive capacity. PLoS ONE 4 (7) : e6104. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0006104
dc.identifier.issn19326203
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/165604
dc.description.abstractBackground: Phenotype and function of regulatory T cells (Treg) largely depend on the presence of the transcription factor FOXP3. In contrast to mice, human Treg cells express isoforms of this protein. Besides the full length version (FOXP3fl), an isoform lacking the exon 2 (FOXP3Delta2) is co-expressed in comparable amounts. Recently, a third splice variant has been described that in addition to exon 2 also misses exon 7 (FOXP3Delta2Delta7). Exon 7 encodes for a leucine zipper motif commonly used as structural dimerization element. Mutations in exon 7 have been linked to IPEX, a severe autoimmune disease suggested to be caused by impaired dimerization of the FOXP3 protein. Principal Findings: This study shows that the lack of exon 7 does not affect (homo-) dimerization. Moreover, the interaction of FOXP3Delta2Delta7 to RUNX1, NFAT and NF-kB appeared to be unchanged in co-immunoprecipitation experiments and reporter gene assays, when compared to FOXP3fl and FOXP3Delta2. Nevertheless, retroviral transduction with FOXP3Delta2Delta7 failed to induce the typical Treg-associated phenotype. The expression of FOXP3-induced surface molecules such as CD25 and CTLA4 were not enhanced in FOXP3D2D7 transduced CD4+ T cells, which also failed to exhibit any suppressive capacity. Notably, however, co-expression of FOXP3fl with FOXP3Delta2Delta7 resulted in a reduction of CD25 expression by a dominant negative effect. Conclusions: The leucine zipper of FOXP3 does not mediate dimerization or interaction with NFAT, NF-kB and RUNX1, but is indispensable for the characteristic phenotype and function in Treg cells. FOXP3Delta2Delta7 could play a role in regulating the function of the other FOXP3 isoforms and may be involved in cancer pathogenesis, as it is overexpressed by certain malignant cells. © 2009 Mailer et al.
dc.publisherPublic Library of Science
dc.sourceUnpaywall 20200320
dc.subjectcytotoxic T lymphocyte antigen 4
dc.subjectimmunoglobulin enhancer binding protein
dc.subjectinterleukin 2 receptor alpha
dc.subjectisoprotein
dc.subjectleucine zipper protein
dc.subjecttranscription factor FOXP3
dc.subjecttranscription factor NFAT
dc.subjecttranscription factor RUNX1
dc.subjectforkhead transcription factor
dc.subjectFOXP3 protein, human
dc.subjectimmunoglobulin enhancer binding protein
dc.subjectisoprotein
dc.subjectleucine zipper protein
dc.subjectprimer DNA
dc.subjectRUNX1 protein, human
dc.subjecttranscription factor NFAT
dc.subjecttranscription factor RUNX1
dc.subjectanimal cell
dc.subjectanimal experiment
dc.subjectarticle
dc.subjectcancer cell
dc.subjectcarcinogenesis
dc.subjectCD4+ T lymphocyte
dc.subjectcell function
dc.subjectcontrolled study
dc.subjectdimerization
dc.subjectexon
dc.subjectgene mutation
dc.subjectgene repression
dc.subjectgene transfer
dc.subjectgenetic transcription
dc.subjecthuman
dc.subjecthuman cell
dc.subjectimmunoprecipitation
dc.subjectIPEX syndrome
dc.subjectmouse
dc.subjectnonhuman
dc.subjectphenotype
dc.subjectprotein binding
dc.subjectprotein expression
dc.subjectprotein function
dc.subjectprotein interaction
dc.subjectprotein localization
dc.subjectregulatory T lymphocyte
dc.subjectreporter gene
dc.subjectRetrovirus
dc.subjectanimal
dc.subjectBagg albino mouse
dc.subjectcell fractionation
dc.subjectchemistry
dc.subjectgenetics
dc.subjectimmunology
dc.subjectmetabolism
dc.subjectnucleotide sequence
dc.subjectphysiology
dc.subjectreverse transcription polymerase chain reaction
dc.subjectMus
dc.subjectAnimals
dc.subjectBase Sequence
dc.subjectCore Binding Factor Alpha 2 Subunit
dc.subjectDimerization
dc.subjectDNA Primers
dc.subjectExons
dc.subjectForkhead Transcription Factors
dc.subjectHumans
dc.subjectLeucine Zippers
dc.subjectMice
dc.subjectMice, Inbred BALB C
dc.subjectNF-kappa B
dc.subjectNFATC Transcription Factors
dc.subjectProtein Binding
dc.subjectProtein Isoforms
dc.subjectReverse Transcriptase Polymerase Chain Reaction
dc.subjectSubcellular Fractions
dc.subjectT-Lymphocytes, Regulatory
dc.subjectTranscription, Genetic
dc.typeArticle
dc.contributor.departmentDEPT OF MICROBIOLOGY & IMMUNOLOGY
dc.description.doi10.1371/journal.pone.0006104
dc.description.sourcetitlePLoS ONE
dc.description.volume4
dc.description.issue7
dc.description.pagee6104
dc.published.statePublished
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